Role of tumor angiogenesis in gallbladder carcinoma: with special reference to thymidine phosphorylase.
BACKGROUND
Angiogenesis plays an important role in tumor growth and metastasis. Thymidine phosphorylase (TP), as well as vascular endothelial growth factor (VEGF), is known to be an angiogenic factor. The aim of this study was to clarify whether TP regulates angiogenesis and to determine the clinicopathological role of TP expression in gallbladder cancer.


METHODS
Thirty-seven patients with gallbladder cancer who underwent curative surgical resection were included in this study, and we evaluated results in 21 of these patients in whom TP gene expression could be measured. Intratumoral TP gene expression was evaluated using the Danenberg tumor profile method. TP gene expression was classified into two groups according to median values: high and low. Tissue TP expression was classified into two groups (positive and negative) by a pathologist. Clinicopathological variables were compared between groups with high and low TP gene expression (TP high and TP low groups).


RESULTS
No correlation was observed between TP gene expression (high and low groups) and any clinicopathological variables except survival rate. However, the survival rate was significantly lower in the TP high group (P<0.05). TP gene expression was associated with tissue TP expression evaluated by immunohistochemical staining (P<0.05). In addition, tumor microvessel density was significantly higher in the TP high group (P<0.05).


CONCLUSIONS
Expression of the TP gene in gallbladder carcinoma is associated with angiogenesis and may be a new independent prognostic parameter.
Harino
Yukari
Y
Department of Surgery, Institute of Health Biosciences, University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
Imura
Satoru
S
Kanemura
Hirofumi
H
Morine
Yuji
Y
Fujii
Masahiko
M
Ikegami
Toru
T
Uehara
Hisanori
H
Shimada
Mitsuo
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005706:Gallbladder Neoplasms / Q000098:blood supply* / Q000201:enzymology*; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D016019:Survival Analysis; D013939:Thymidine Phosphorylase / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D013939:Thymidine Phosphorylase